1. Field of the Innovation
The present innovation relates generally to the fields of biophysics, bioelectromechanics, tissue regeneration, tissue culture, and neurophysiology. More specifically, the present innovation relates to the use of an electromagnetic field, and preferably, a time-varying magnetic field, for modifying, potentiating or controlling the growth and specific genetic expression of biological cells and tissue, such as mammalian tissue. More specifically, the present innovation relates to the use of a noninvasive method and apparatus comprising relatively low frequency magnetic fields for modifying the genetic regulation of mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination.
2. Background and Related Art
Cartilage is a type of dense connective tissue existing within many joints and is composed of specialized cells called chondrocytes that produce a large amount of extracellular or cartilaginous matrix comprised of actin and collagen fibers, proteoglycans, glycosaminoglycans, and elastin fibers. Chondrocytes are the only cells found in cartilage.
Unlike other connective tissues, cartilage does not contain blood vessels or is referred to as avascular. Thus, compared to other connective tissues, cartilage grows and repairs more slowly.
There are several diseases which can affect the cartilage. Chondrodystrophies are a group of diseases characterized by disturbance of growth and subsequent ossification of cartilage. Osteoarthritis (OA) is a common disease affecting cartilage.
Cartilage has limited repair capabilities, because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Therefore, if damaged, cartilage is difficult to heal. Also, because hyaline cartilage does not have a blood supply, the deposition of new cartilaginous matrix is slow.
Acetaminophen/paracetamol is generally used as a first line treatment and anti-inflammatory drugs (NSAIDs) are only recommended as add on therapy if pain relief is not sufficient. There is a need to find definitive answers and to develop procedures that relieve arthritis symptoms and produce a durable replacement for damaged cartilage.
Bones are rigid organs that form part of the endoskeleton of vertebrates. One of the types of tissue that makes up bone is the mineralized osseous tissue, also called bone tissue, which gives it rigidity and a honeycomb-like three-dimensional internal structure.
There are several types of cells constituting the bone. For example, osteoblasts are mononucleate bone-forming cells that descend from osteoprogenitor cells. They are located on the surface of osteoid seams and make a protein mixture known as osteoid, which mineralizes to become bone. Osteoid is primarily composed of Type I collagen.
In the disease commonly known as osteoporosis, bone demineralizes and becomes abnormally rarefied. Diminished bone density may lead to vertebrae collapse, fractures of hips, lower arms, wrists, ankles as well as incapacitating pains.
Current therapies comprise invasive procedures (e.g. surgery or drug administration) as opposed to the described innovation which is a non-invasive procedure. Alternative nonsurgical therapies for such diseases include electrical bone growth stimulation comprised of electric and magnetic field therapies. However these therapies are moderately invasive as they rely on either skin contact or insertion of probes/electrodes into the tissues.
Nucleus pulposus is the jelly-like substance in the middle of the spinal disc that functions to distribute hydraulic pressure in all directions within each disc under compressive loads. The nucleus pulposus comprises disc chondrocytes (as opposed to articular chondrocytes), collagen fibrils, and proteoglycan aggrecans that have hyaluronic long chains which attract water. Attached to each hyaluronic chain are side chains of chondroitin sulfate and keratan sulfate.
Electric and Magnetic Fields
An electric field is a property that describes the space that surrounds electrically charged particles. Electric fields are created by differences in electric potential or voltage: i.e., the higher the voltage, the stronger will be the resultant electric field. In contrast, magnetic fields that are generated electromagnetically are created when electric current flows: i.e., the greater the current, the stronger the magnetic field. An electric field will exist even when there is no current flowing. In contrast, a magnetic field generated electromagnetically will not exist when there is no current. If current does flow, the strength of the magnetic field that is generated electromagnetically will vary with power consumption but the electric field strength will be constant. Resultant forces are related to both electric and magnetic fields. The force associated with an electric field depends on a stationary or static charge. Conversely, the force exerted on a charged particle associated with a magnetic field (i.e., Lorentz force) depends on a moving charge. Further, electric and magnetic fields are not entirely mutually exclusive. For example, charged particles do not only produce electric fields. As charges move, they generate magnetic fields, and if the magnetic field changes, the change in said magnetic field will generate electric fields. Thus weak metals (ions) such as CA2+, K+, Li+, and Mg2+ are all subject to modulation or resonance effect and can be made to move sub-cellularly due to magnetic flux. Stated differently, a changing magnetic field gives rise to an electric field. In nature lightning is an example of an atmospheric electrical discharge that creates an attendant magnetic field.
Electrical Stimulation Therapies
Electrical stimulation therapies include: capacitive coupling (CC); and direct current (DC) or direct coupling. The original basis for forms of electric stimulation therapy was the observation that physical stress on bone causes the appearance of tiny electric currents (i.e., a piezo-electric effect) that, along with mechanical strain, were thought to be the mechanisms underlying transduction of the physical stresses (compression and tension) into an electrical signal that promotes bone formation. CC relies on an electric field that is generally generated by 2 capacitive plates or electrodes placed on a patient's skin on opposite ends of a region of interest to apply electrical stimulation in the region of interest. DC-based therapies require the placement of opposing electrodes in direct contact with the skin surface surrounding the tissue of interest (Trock, 2000) and generally involve implantation of the electrodes. The region of interest is stimulated by a constant direct current.
Magnetic Field Therapies
Magnetic field therapies include: time-varying magnetic field (TVMF) therapies including pulsed electromagnetic field (PEMF) therapies. The general use of time-varying magnetic fields to stimulate the growth of cells has been disclosed in the related art. It has been theorized that the piezo-electric properties in human tissue such as bone and cartilage forms the basis for regulating bone and cartilage formation. Specifically, because a magnetic field imposes a force on magnetic particles and moving electrically charged particles, the magnetic field forces simulate physical stress in human tissue thereby resulting in small, induced currents (Faraday currents) in the tissue's highly conductive extracellular fluid. In general, time-varying magnetic field therapies involve the use of coils to electrically generate a magnetic field. PEMFs are considered a subset of time-varying magnetic field therapies and are generally associated with pulses or bursts in its waveforms. Resultant waveforms used in PEMF therapies can be substantially monophasic, substantially biphasic, substantially square, sinusoidal, or substantially triangular. Further, PEMF therapies are generally comprised of frequencies on the lower end of the electromagnetic spectrum such as from 6-500 Hz. Further, waveforms used in PEMF therapies generally have high rising and falling slew rates on the order of Tesla/sec, thereby promoting said pulses or bursts.
In U.S. Pat. No. 7,179,217 an apparatus for enhancing tissue repair in mammals is disclosed. The disclosed apparatus comprises: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating a magnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and a means for supplying the electrically conductive coil with a square wave time-varying electrical current sufficient to create a time-varying magnetic force of from approximately 0.05 G to 0.5 G within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time-varying magnetic force of from approximately 0.05 G to 0.5 G is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time-varying magnetic force. The electrically conductive coil is preferably a ferromagnetic material, such as wire, with approximately ten windings per inch. The sleeve can be placed on a body part, e.g. an arm or a leg, of the mammal and the body part exposed to the 0.05 G to 0.5 G time-varying magnetic force for an extended period of time to enhance tissue repair, such increasing the healing rate of bone fracture repair or increased healing rate of ulcerated skin. It is preferable that the treated mammal is provided an increased level of calcium ions (Ca+ or Ca++) during the application of the time-varying magnetic force.
Anabolic and Catabolic Gene Expressions
In recent decades, many more hormones with at least some effects have been discovered, including cytokines or paracrine and autocrine factors which are the products of genomic up or down regulations. Further specific genes and some molecules work in concert with each other or in gene cascades (chaperones) which facilitate the end goal of tissue remodeling, with processes such as glucose metabolism fluctuating to match an animal's normal periods of activity throughout the day (Ramsey, et al., 2007).
Similarly, known biomolecules such as vitamins are useful in perpetuating the process of normal cartilage and bone maintenance. Vitamin D (specifically D3) and Vitamin K are known to a degree in relation to normal mammalian (specifically human) physiology (Atkins, 2009), (Koshihara, 1997). The inventors postulate that due to the facilitated stimulation of important gene expressions (specifically osteocalcin up-regulation which was unanticipated as part of the responding cascade) that addition of increased concentrations of these two vitamins during treatment of the affected area (ROI) in any outlined regime or matrix will further enhance and accelerate the formation of new bone and differentiate the expression of bone from cartilage in the subject tissue as mineralization will produce bone and not cartilage.
Anabolism is the set of metabolic pathways or genomic and protein responses that construct molecules from smaller units (de Bolster, 1997). These reactions require an energy system which in the case of cells is derived from other genomic responses in the breakdown of energy “packets” in the cell. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as anabolic or as catabolic, which is the opposite of anabolic.
Catabolism is the set of pathways that break down molecules into smaller units and release energy (de Bolster, 1997). In catabolism, large molecules such as nucleic acids, proteins, polysaccharides, and lipids, and are broken down into smaller units such as amino acids, nucleotides, monosaccharides, and fatty acids, respectively. For the purposes herein, “catabolic” will be associated with a reparative function and specifically, the breakdown, reorganization, or the degeneration of tissue from an organic perspective.
Currently, full advantage is not being taken of the use of these biophysical and electrical stimuli. However, as the underlying mechanisms at the molecular and cellular level become understood, medical instrumentation using this medical technology will become more widely implemented. Currently, the related art primarily depends on frequency and B-Field magnitude associated with an electromagnetic field waveform for the stimulated growth of biological cells and associated tissue. In fact, related art publications indicate that a B-Field magnitude is the primary control variable for affecting biological cell and tissue growth. At some point, the B-field magnitude's effect becomes more of a thermal effect as compared to a physical force imparted at the cellular level. For example any magnetic field greater than 30 kHz falls into the radio frequency range and is known to result in thermal heating effects at the sub-cellular level. The related art is deficient in discovery of a specific stimulation field profile necessary for up-regulating and down-regulating specific genes, wherein said profile is comprised of not only frequency and B-Field magnitude, but also waveform shape, rise time, rising slew rate, fall time, falling slew rate, duty cycle, dwell time, time of exposure, and other possible factors. The therapeutic implications of the discovery of specific profiles associated with stimulating specific genes will be explained herein. Thus, it would be desirable to provide an apparatus and method of use which would promote the stimulation of specific genes by a specific stimulation field of predetermined profile.